Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3

CONTEXT: Congenital deficiency of the neuroendocrine-specific enzyme prohormone convertase (PC) 1/3 leads to a syndrome characterized by obesity, small intestinal dysfunction, and dysregulation of glucose homeostasis in humans. To date, only two unrelated subjects with this disorder have been reported. Research DESIGN AND METHODS: We now report a third proband, a 6-yr-old boy, offspring of a consanguineous union of parents of North African origin, who was homozygous for a novel missense mutation Ser307Leu. We characterized the functional properties of the mutant PC1/3 and characterized the clinical phenotype of the patient. RESULTS: In vitro this mutation markedly impairs the catalytic activity of the convertase. However, in contrast to other previously described naturally occurring mutations, intracellular trafficking of this mutant enzyme appeared normal. The Ser307Leu mutant retained some autocatalytic activity, even though it was completely inactive on other substrates. As with the previous two patients, this child had obesity and persistent diarrhea, however, there was no history of reactive hypoglycemia. The patient showed markedly increased food intake at an ad libitum test meal, confirming that hyperphagia makes a major contribution to the obesity seen in this syndrome. CONCLUSION: This case extends the clinical and molecular spectrum of human congenital PC1/3 deficiency.     

Performance evaluation of ion exchange and affinity chromatography for HbA1c estimation in diabetic patients with HbD: a study of 129 samples

ObjectivesTo compare ion exchange and boronate affinity chromatography for HbA_1c estimation in patients with type I and II diabetes having hemoglobin D.Design and methodsSystems based on ion exchange and boronate affinity chromatography were evaluated and compared for their performance for HbA_1c estimation in patients with homozygous and heterozygous D disease.ResultsBoronate affinity chromatography shows least interference by HbD in heterozygous as well as homozygous diabetic patients for HbA_1c estimation.ConclusionsThe use of boronate affinity chromatography was found to be helpful in evaluating glycemic control in diabetic subjects with HbD.     

Sex differences in the adequacy of pain management among patients referred to a multidisciplinary cancer pain clinic

Few studies have evaluated sex differences in the adequacy of pain management in cancer. Existing studies have been marked by methodological limitations and results have been mixed. The present study sought to determine whether sex was associated with pain severity and pain management in cancer patients newly referred by their primary oncology team to a multidisciplinary cancer pain clinic. One hundred thirty-one cancer patients completed the Brief Pain Inventory-Short Form and medical chart review was conducted to obtain patients' clinical characteristics and pain treatment data. There were no differences between males and females in ratings of worst pain in the last week. Females were significantly less likely to have been prescribed high potency opioids by their primary oncology team and significantly more likely to report inadequate pain management as measured by Pain Management Index scores. These results suggest a sex bias in the treatment of cancer pain and support the routine examination of the effect of sex in cancer pain research.     

Investigation of tRNALys/Leu and ATPase 6/8 gene mutations in Iranian ataxia telangiectasia patients

Introduction

Ataxia telangiectasia (AT) is a rare human neurodegenerative autosomal recessive multisystem disease. AT is the result of mutations in the AT-mutated (ATM) gene. ATM protein is required for radiation-induced apoptosis and acts before mitochondrial collapse. The tRNA genes are considered one of the hot spots for mutations causing mitochondrial disorders. Due to the important role of ATM in apoptosis and its effect on the cell cycle it might be possible that it has a central role in mtDNA mutations. On the other hand, the tRNA^Lys/Leu gene and also ATPase6 and ATPase8 genes are important for many mitochondrial diseases and many causative mutations have been reported from these genes.

Material and methods

In the present research, we performed mutation screening for these genes in 20 patients who were diagnosed with ataxia telangiectasia by a PCR sequencing method.

Results

The results showed a significant level of mtDNA variations in AT patients. Among 20 patients in this study, 12 patients (60%) were detected with point mutations, among which 8 mutations (40%) belonged to the MT-ATP6 gene. There was probably a second effect of mtDNA mutations in AT disease and mtDNA plays a main role in establishment of AT.

Conclusions

MtDNA mutations might be responsible for the decline of mitochondrial function in AT patients. Mitochondrial investigation can help to understand the mechanism of damage in AT disease.     

The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals

BACKGROUND: Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation. METHODS: We assessed the association between the V103I polymorphism in the MC4R gene and obesity in three UK population based cohort studies, totalling 8304 individuals. We also did a meta-analysis of relevant studies, involving 10 975 cases and 18 588 controls, to place our findings in context. FINDING: In an analysis of all studies, individuals carrying the isoleucine allele had an 18% (95% confidence interval 4-30%, P=0.015) lower risk of obesity compared with non-carriers. There was no heterogeneity among studies and no apparent publication bias. INTERPRETATION: This study confirms that the V103I polymorphism protects against human obesity at a population level. As such it provides proof of principle that specific gene variants may, at least in part, explain susceptibility and resistance to common forms of human obesity. A better understanding of the mechanisms underlying this association will help determine whether changes in MC4R activity have therapeutic potential.     

A dual contrast injection technique for multidetector computed tomography angiography of Fontan procedures

Extracardiac and lateral tunnel Fontan palliations result in caval venous return to the branch pulmonary arteries without prior blood mixing in the right atrium. Single contrast injection techniques result in suboptimal pulmonary computed tomography angiography since blood streaming results in asymmetric pulmonary flow of injected contrast. We used a dual injection technique--dorsal foot vein and upper extremity vein to achieve optimal simultaneous opacification of the inferior and superior venae cavae and branch pulmonary arteries. The resulting dataset allowed for excellent 3D volume renderings and multiplanar reformat images useful for stenosis, aneurysm, and metal stent evaluation.     

Effect of Ultrasonic Surface Mechanical Attrition Treatment-Induced Nanograins on the Mechanical Properties and Biocompatibility of Pure Titanium

Commercially pure titanium (Ti) is widely used in bio-implants due to its high corrosion resistance. However, Ti exhibits marginally low mechanical and tribological properties, which limit its applications in some orthopedic implants. In this work, the Ti samples were subjected to ultrasonic surface mechanical attrition treatment (SMAT) for various durations to improve their surface properties such as hardness, strength and surface energy. SMAT-induced grain refinement was analyzed using optical, scanning electron and atomic force microscopy techniques. A Vickers hardness test was performed to determine the through-thickness hardness. Mechanical testing was carried out to measure the yield strength, ultimate tensile strength and ductility of the specimens. Corrosion tests were performed on a Gamry Potentiostat. The surface energy of SMAT-modified samples was calculated using the Owens–Wendt method. It was observed that SMAT reduced the average grain size from 50 μm to as low as 100 nm. The grain refinement and the corresponding grain boundary density led to a significant improvement in mechanical properties and biocompatibility in terms of increased hardness, yield and tensile strengths, surface energy, corrosion rate and hydrophilicity.     

Removal of hexavalent chromium ions using micellar modified adsorbent: isothermal and kinetic investigations

Hexavalent chromium is a very poisonous oxyanion and has had a negative impact on human health. This study assessed the viability of removing chromium(vi) using micellar modified adsorbents. In this study, chromium(vi) was removed from locally accessible wheat bran using separate applications of anionic sodium dodecyl sulfate (SDS) and cationic cetyltrimethylammonium bromide (CTAB) surfactants. The initial chromium content (5–12 ppm), pH (2–12), adsorbent dose (1–6 g/100 mL), agitation time (15–240 min), agitation speed (50–300 rpm), and temperature (15–50 °C) were all varied in the adsorption investigation. Pseudo first-order and second-order kinetic models were utilized to analyze the kinetic investigation. To determine thermodynamic parameters, the van''t Hoff relationship was used. The maximum result for chromium(vi) uptake was obtained as 87.7%, 83.5% and 98.9% for WB, SDS-mWB, and CTAB-mWB, respectively, at an agitation time of 240 min (i.e., 4 h), temperature (i.e., 25–30 °C), agitation speed (150 rpm). However, both WB and CTAB-mWB derives metal ion removal at lower pH levels (2–4), whereas SDS-mWB requires a pH between 4 and 6 for maximum percentage removal of Cr(vi). The equilibrium data of WB and SDS-mWB were modeled by the Langmuir adsorption isotherm, while the data of CTAB-mWB fitted well in the Freundlich isotherm model. The kinetic analysis of WB, SDS-mWB, and CTAB-mWB revealed that the pseudo-second-order kinetic model provides a thorough explanation for each of these adsorbents. It was found that CTAB-mWB can preferably be used for the removal of chromium(vi) due to its high affinity with adsorbate molecules and adsorption capacity.

In this investigation, anionic sodium dodecyl (SDS) and cationic cetyltrimethylammonium bromide (CTAB) surfactants were separately applied to locally accessible wheat bran to remove chromium(vi).